The elevated high-density lipoprotein (HDL) cholesterol concentrations of long distance runners has been ascribed almost exclusively to increased muscle lipoprotein lipase. Based on data collected in cross- sectional and longitudinal studies, we have proposed an alternative theory: long-distance runners have the HDL-cholesterol metabolism of men who are below their sedentary weight rather than the HDL-cholesterol metabolism of lean sedentary men who are at their usual sedentary weight. In other analyses, we have found that the most significant determinant of male runners' plasma HDL-cholesterol concentrations is the difference between the runners' greatest weight and their current weight. HDL- cholesterol levels were highest in runners who had lost the most weight, i.e., highest in those who are presumed to be the furthest below their weight set-point. We therefore propose to investigate the differences in diet, fat cell morphology and lipoprotein metabolism in previously- overweight and naturally lean men and women who run and who live sedentary lifestyles in a cross-sectional study to better understand the relationship between lipoprotein metabolism and weight set-point. Runners and sedentary men and women will be measured for lipoprotein cholesterol, triglycerides, polyacrylamide gel electrophoresis of HDL and low-density lipoprotein subclasses, apolipoproteins A-I and B, intravenous fat clearance rate, post-heparin lipoprotein lipase and hepatic lipase, adipose tissue lipoprotein lipase, cholesteryl ester transfer activity, diet, percent body fat, and regional adiposity. The survey will: 1) confirm or reject the weight set-point hypothesis we have proposed; 2) provide a possible explanation of the lipoprotein differences between male and female runners; 3) elucidate the mechanism for the lipoprotein changes that occur during exercise-induced weight loss. These observations may refine our understanding of the weight set- point concept.